ES2376330T3 - PHYSIOLOGICALLY ACTIVE COMPOSITION AND PROCEDURE TO PRODUCE THE SAME. - Google Patents

Abstract

A stretch-oriented multilayer film suited for use as a freeze packaging material, a deep drawing packaging material, a vertical pillow packaging material, etc., is provided as a stretch-oriented multilayer film, comprising at least three layers including a surface layer (a) comprising a thermoplastic resin, an intermediate layer (b) comprising a polyamide resin and a surface layer (c) comprising a sealable resin, said multilayer film exhibiting an impact energy of at least 1.5 Joule at a conversion thickness of 50 mum at -10° C. The multilayer film is produced through an inflation process using water having a large capacity as a cooling and a heating medium and including a combination of a high degree of stretching and a high degree of relaxation heat treatment not exercised heretofore.

Description

Physiologically active composition and procedure to produce it

Technical field

The present invention relates to a composition that has physiological activity, such as an antitumor effect and a hypoglycemic effect. Specifically, it refers to a physiologically active composition that includes an extract composition of more than two kinds of fungi selected from a fungus belonging to basidiomycetes and one from a plant root belonging to Araliaceae, as described below.

Prior art

It has long been known that a carpophore or a mycelium culture (which includes a mixture of a mycelium and a culture in addition to the mycelium alone and, hereafter referred to simply as a culture) of a lacquered pipe belonging to the Basidiomycetes is a medicinal herb and has several medical benefits and a component contained therein, which includes polysaccharides, has a certain type of antitumor effect. Similarly, several physiologically active substances, including one with antitumor activity, were also extracted from a turkey tail carpophore belonging to basidiomycetes. Additionally, a root of a plant belonging to Araliaceae that includes ginseng and an extract composition thereof as a medicinal herb has long been known, and many medical benefits of it are also known. It is also known that a carhell of Phellinus linteus belonging to the genus Phellinus and basidiomycetes and that an agaric belonging to Agariacaceae contain useful saccharides such as 1-glucan (Japanese unreleased published patent application No. 2003-183176).

Disclosure of the invention

An effective component, such as an active antitumor component in the medicinal herbs described above, has not yet been clarified. The efficacy and synergistic effects in a mixture of these medicinal herbs have not yet been scientifically clarified, so predicting their effectiveness is difficult.

The present inventor has discovered that a composition formulated with an extract component derived from several fungi belonging to basidiomycetes and an extract component derived from a root of a plant belonging to Araliaceae as described below show an oxide-reduction potential, whose magnitude expresses physiological activity such as the antitumor effect and reduction of blood glucose levels (hereinafter, this effect is called hypoglycemic effect) in a hyperglycemic patient and completed the invention.

The present invention is directed to a physiologically active composition, which contains: An extract component of a carpophore of the following basidiomycete fungi: Ganoderma lucidium, Coriolus versicolor and Phellinus linteus; and an extract component of a root of P. japonicus CA Meyer belonging to Araliaceae, in which the ratio between Ganoderma Lucidum: Coriolus Versicolor: Phellinus Linteus: P. japonicus CA Meyer in the raw material for extraction is 1: 1: 1 : 1 by weight and in which the oxide-reduction potential of the aqueous solution of the composition is not greater than 330 mV.

The pH of an aqueous solution of the composition is preferably not less than 4.5 and not more than 6.5.

In the composition of the invention, the extract composition of a carpophore of basidiomycete fungi and the extract component of a root of a plant belonging to Araliaceae are, respectively, components extracted with hot water.

The present invention is also directed to a pharmacological formulation that is mixed when used and provided with a first drug comprising a hot water extract component from a carphor, a mycelium and a culture of Ganoderma lucidum, Coriolus Versicolor and Phellinus linteus , and a second drug comprising a hot water extract component from a root of

P. japonicus CA Meyer, in which the ratio between Ganoderma Lucidum: Coriolus Versicolor: Phellinus Linteus: P. japonicus CA Meyer in the raw material for extraction is 1: 1: 1: 1 in weight and in which the potential of The reduction of an aqueous solution of the formulation is not more than 330 mV.

The present invention is further directed to a method of preparing a physiologically active composition, which comprises the steps of extracting with a hot water a carpophore of Ganoderma lucidium and Coriolus Versicolor; extract with a hot water a carpophore of Phellinus linteus; extract a root of P. japonicus CA Meyer with hot water, in which the ratio between Ganoderma lucidum: Coriolus Versicolor: Phellinus Linteus: P. japonicus CA Meyer in the raw material for extraction is 1: 1: 1: 1 by weight , and mix the extract components with the hot water obtained in the extraction stages.

The present invention is also directed to a method of preparing the physiologically active composition, comprising the steps of: obtaining a hot water extract of a Ganoderma lucidium and Coriolus versicolor carpophore, a hot water extract of a Phellinus linteus carpophore and a hot water extract of a P. japonicus CA Meyer root separately or from the same extraction system with respect to at least more than two kinds of hot water extracts, in which the ratio between Ganoderma Lucidum: Coriolus Versicolor : Phellinus Linteus: P. japonicus CA Meyer in the raw material for extraction is 1: 1: 1: 1 by weight, so that a composition comprising the hot water extract component of a carpophore of Ganoderma lucidium and Coriolus is prepared Versicolor, the hot water extract component of a Phellinus linteus carpophore and the hot water extract component of a P. japonicus CA Mey root er.

Best way to carry out the invention

The best way to carry out the present invention is described below.

[Fungi belonging to Basidiomycetes Aphyllophorales Ganoderma Ganodermaceae and fungi belonging to Aphyllophoarles Polyporaceae Coriolus]

In the present invention as an active component there is an extract obtained from the carpophore of more than two kinds of fungi belonging to these genera.The fungi belonging to Ganodermaceae and Coriolous are used in combination.

In Ganodermaceae the Reishi mushroom (Ganoderma Lucidum) is used. The Reishi mushroom is preferably grown in the nature in trees, but rarely autogenous. Reishi mushroom can be grown artificially. The Reishi mushroom has a waxy hat section and a stem section, whose length reaches approximately 15 cm. The color of the carpophore is red, blue, yellow, White, purple or black. This fungus grows on a stump or near the base of a tree weakened by a disease and forms a white protonema.

Coriolus Versicolor is used as Coriolus. Coriolus Versicolor grows naturally in the western part of Japan, particularly in the regions of Shinshu (specifically Nagano Prefecture), Shikoku and Kyushu. Coriolus Versicolor is a xylophile fungus and, particularly xylophile in broadleaf trees.

[Fungus belonging to Hymenochaetaceae Phellinus Agarical Basidiomycetes]

Phellinus linteus is used as a basidiomycete fungus belonging to the genus Phellinus.

The natural Phellinus linteus is a bright yellow or yellow-brown wood fungus that is a parasite of the mulberry and that generates a semicircular carpophore. In Chinese medicine this fungus is called Sang-Hwang.

Basidiomycetes are not particularly limited but may include natural growth fungi wild, artificially grown fungi or cell-grown fungi. Fungi growing from wild natural way. Preferably, the carphor is dried in air at room temperature and protected from light.

Particularly with the Ganodermaceae fungus, the mature black carpophore of natural form. With the Coriolus fungus, the autogenous carpophore taken in summer is preferred and, more preferably, it was taken to air at room temperature and protected from light.

[Araliaceae plant root]

The composition of the present invention also includes an extract composition of a plant root belonging to the Araliaceae family as an active component. Japanese ginseng is used as an araliaceae plant (Zhuzishen ginseng, P. Japonicus C. A. Meyer) - The root is used.

[Composition preparation procedure]

The composition of the present invention is obtained by first extracting the basidiomycete fungus with hot water, including the Ganodermaceae, Coriolus and Phellinus fungi described above, and the root of an araliaceae plant described above. The component of the raw material in the composition comprises the combination of fungi described above. Each raw material or a combination of more than two kinds of materials raw can be extracted with hot water to obtain the extract components of the fungi basidiomycetes and from the root of araliaceous plant separately, which, later, can be mixed. Or both basidiomycete fungi As a root of an araliaceous plant as raw material they are extracted together with hot water. Preferably all the raw materials for the extract component that will contain the composition are mixed and then extract with hot water. In hot water extraction, each raw material is preferably crushed into small or powdered pieces and, more preferably, in small pieces. Crushing into small pieces of a cover of approximately 5 mm or shorter lateral is particularly preferable.

In the raw material for extraction, the amount of the basidiomycetes and that of the root of an araliaceous plant in a gender unit used are equal to each other by weight. For example, when Ganodermaceae, Coriolus and Phellinus mushrooms are used as basidiomycete fungi and Japanese ginseng as the araliaceae plant, an equal amount can be extracted, for example from 4 to 7 g of each material, with 1000 ml of hot water.

When the composition is prepared with the raw material for extraction in a formulation ratio (weight ratio) of 1: 1: 1: 1 of the Ganodermaceae carpophore. Coriolus Carpophore: Phellinus Carpophore: Japanese Ginseng (root), which is a composition of the present invention, for example, 6 g of the Ganodermaceae carpophorus, g of the Coriolus carpophore, 6 g of the Phellinus carpophore and 6 g of Japanese ginseng, mixed and crushed into small cubic pieces of approximately 5 mm side, to which 500 to 1000 ml of distilled water are added and boiled for three hours after using a reflux condenser and then , is filtered to give the composition (stock solution) used in the present invention.

The temperature of the hot water for extraction is 80 ° C to 100 ° C, preferably 90 ° C to 95 ° C. The extraction time is preferably at least one hour, more preferably more than 2 hours, still more preferably more than 2.5 hours. An upper limit for the extraction time is 3 to 4 hours. The extraction operation is preferably carried out using a reflux condenser. An amount of water for the raw material for extraction is not particularly limited, but preferably 500 parts by weight to 1000 parts by weight of water are used to extract from 10 parts by weight to 30 parts by weight of the raw material. An extracted liquid obtained in the extraction with this proportion by weight (particularly in the case where the reflux condenser is used) forms a liquid with a concentration suitable for administration without modifying.

The extracted liquid obtained is filtered to remove residual raw material for extraction. A filtrate or liquid supernatant of the extracted liquid is concentrated to give a concentrated liquid if necessary. The water in the extracted liquid can be evaporated to give a solid extract component (powder type) and the extract component is dried to give a desired dry extract component if necessary.

Additionally, when considering the dosage mode and the dosage form of the composition, an additive can be added for the preparation of the drug or stabilization of the extract component during concentration or drying.

Additionally, a stock solution of this composition can be properly diluted and used as the composition of the present invention. A dilution ratio can be set as necessary and the stock solution is diluted approximately in a range of twice to three hundred times. Preferably, the dilution ratio is used from twice to twenty times, more preferably from four times to sixteen times. The dilution medium is not particularly limited, but preferably it is water.

Also, a solvent in this stock solution can be removed by a suitable drying process to obtain the solid extract component described above, which is used as the composition of the present invention.

The composition may be composed of pharmacological products that are mixed when used. That is, a first drug that contains the basidiomycete extract component and a second drug that contains the root extract component of an araliaceous plant can be combined to mix when used. Each of the drugs, first and second, may be in the form of an aqueous solution or a solid, such as a powder.

The composition prepared in this way is used when the oxidation-reduction potential of its solution is less than 330 mV.

In particular, the composition with this range of the oxidizing-reduction potential is preferably used as the active antitumor composition and the hypoglycemic agent composition. The oxidizing-reduction potential is measured in an aqueous solvent, preferably in water. The stock solution obtained by extraction or its dilute aqueous solution can be used unchanged to measure the potential for oxidization-reduction. When the composition solidifies, it is dissolved or suspended with a suitable solvent or water for measurement.

The oxidation-reduction potential of a solution of the composition is preferably less than 300 mV, still more preferably less than 250 mV. More preferably, less than 0 mV. The oxidizing-reduction potential is preferably greater than -1200 mV, more preferably, greater than -300 mV.

The pH value of an aqueous solution of the composition is preferably greater than 4.5 but less than 6.5. A mild acidity of the pH is suitable for a living cell, so that the active component of the composition can function more effectively. The composition obtained by extracting each raw material for extraction with hot water generally has a pH greater than 4.5, but less than 6.5 as the stock solution.

The composition of the present invention does not exclude a form containing other active components. Other active components may be contained, provided that a synergistic effect of two kinds of the composition of the extract in the composition of the present invention is not hindered. These active components can be an artificially prepared product based on the extraction component or its composition. The disclosure of the present invention intends, in particular, the active component extracted from a natural product, but naturally it intends a chemically synthesized active component that expresses the effect described herein.

The composition of the present invention has antitumor activity, particularly against leukemia, cervical cancer, lung cancer, ovarian cancer, breast cancer (including metastatic cancer) and skin cancer (including metastatic cancer). Leukemia includes erythroblastic leukosis. The composition of the present invention can be used as an antitumor drug, not only in humans but also in a wide range of mammals, such as cows, horses, dogs and cats. Until now, the antitumor activity of the basidiomycete extract component has been known and the antitumor activity of the root extract component of an araliaceous plant has been confirmed. However, it has already been confirmed that the composition of the present invention shows a higher antitumor activity than expected compared to the antitumor activity of each component separately. The composition of the present invention also has a hypoglycemic effect. This hypoglycemic drug expresses an effect on both insulin-dependent and non-insulin-dependent diabetes mellitus. In addition, the composition of the present invention has a hypotensive action against humans and can be used to treat hypertension and serve as prophylaxis thereof. The composition of the present invention also has a decrease in total blood cholesterol and a decrease in neutral blood fat in humans, etc., and, therefore, can be used to treat hyperlipidemia and serve as prophylaxis. Of the same.

In addition, the composition of the present invention has no adverse effect but properties of reduction or cancellation of the side effects of another drug. In particular, when used as an antitumor drug, in addition to the cure or degeneration of the tumor, various effects such as pain reduction, appetite improvement and good sleep can be achieved. When used as a hypoglycemic drug, in addition to reducing blood glucose levels, effects such as relief of body pain, in particular a considerable improvement of headaches and numbness of the limbs, improvement of appetite, recovery of appetite, can be achieved vision, decreased stress and comfortable sleep.

The components of the extract of the basidiomycete fungi and an araliaceous plant, which are the active components in the present invention, are mixed with a pharmaceutically acceptable carrier or additive to be used as the composition suitable for administration. One form of the composition is not particularly limited, but it can be a liquid drug, a syrup, a suspending agent, a powdered drug, a granule, a tablet, a pill, a capsule, an emulsion, a troccus, a formulation Chewable, a suppository, an eye drop, an injectable solution, an aerosol and an elixir. A solid (powder), which can be converted into a liquid formed by the addition of water when used, is also preferable.

The composition of the present invention can also be administered orally or parenterally. Preferably, it is administered orally. A typical dose in oral administration is described below. The dose is adequately determined according to the symptoms and physical strength of an individual. That is, as a typical dose (usual dose) of, for example, an extract component of 200 mg to 2 g of the basidiomycete fungus and 100 mg to 1 g of an arial plant root per kg of body weight per day is administer by dividing it into one to three times a day. In particular, when used as an antitumor drug, a dose of the extract component of 0.25 to 0.35 g of both the basidiomycete fungus and a root of an araliaceae plant / kg body weight / day is preferable. When used as a hypoglycemic drug, a dose of the extract component of 0.12 to 0.18 g of both the basidiomycete fungus and 0.12 of the root of an araliaceae plant / kg body weight / day is preferable. When used as a hypoglycemic drug, the administration of water and / or alcohol extract from the root of an araliaceous plant is preferably involved. This alcohol extract can be obtained by crushing the root of an araliaceous plant, preferably a ginseng, more preferably, a Japanese ginseng, in small pieces or powder (preferably small pieces of a bucket of approximately 5 mm side) and adding, for example , from 300 to 600 parts by weight of a 40% alcohol solution to 10 to 20 parts by weight of the crushed parts for heating to 80 to 100 ° C for extraction until the alcohol component is substantially evaporated.

The composition of the present invention has an extremely low toxicity and does not express any serious side effects so that a large dose can be administered safely according to the symptoms. A preferred form of the drug for oral administration is a liquid drug or syrup. Water is preferred as medium.

Example

The present invention is described below with illustrative examples, but it should not be construed that these examples limit the scope of the present invention.

[Measurement of the oxide potential-reduction of the composition]

As a raw material, a carpophore of Ganoderma Lucidum, a carpophore of Coriolous Versicolor, a root of Japanese ginseng (P. japonicus C. A. Meyer), a carpophore of Phellinus linteus and a carpophore of Agaricus blazei 5 Murili (Japanese name Kawariharatake) were used. Each used carphor was dried.

The raw material was prepared using the composition of Table 1 below and each one was triturated in a shorter bucket of 5 mm side or smaller, to which 1000 ml of water subjected to ion exchange was added ( purity less than 1 S / cm) and was refluxed for two hours after fixing a reflux condenser for extraction. After extraction, the mixture was filtered to give several formulated solutions. The oxidation-reduction potential and the pH of the various formulated solutions obtained were measured at the time the formulation was prepared, as well as at times after storing the formulation in a 25 ° C incubator and a relative humidity of 14%. for 1, 2, 3 and 4 days. The oxidizing potential and the pH were measured with an HM-14P peachmeter from TOA Radio Wave Industry Co., Inc. The oxidizing potential and is based on the value

15 indicated by the measuring instrument to which the value indicated by the reference electrode is added. The results are shown in tables 2 and 3.

Table 1

Component

 Formulated liquid 1 Formulated liquid 2 Formulated liquid 3 Formulated liquid 4 Formulated liquid 5 Formulated liquid 6 Formulated liquid 7

Reishi

6 6 6 6 6

CoriolousVersicolor

6 6 6

P. japonicus CAMeyer

6 6 6 6 6

PhellinusLinteus

6 6 6

AgariousblazeiMurill

 6 6 6

Unit: g

Table 2

Oxidizing potential-reduction mV

At the time of preparation After 1 day After 2 days After 3 days After 4 days

Formulated liquid 1

297 348 351 332 301

Formulated liquid 2

283 361 288 225 -

Formulated liquid 3

257 320 299 228 283

Formulated liquid 4

187 280 -301 - -

Formulated liquid 5

248 322 398 388 48

Formulated liquid 6

304 362 274 295 330

Formulated liquid 7

219 272 250 92.5 -321

Table 3

pH

At the time of preparation After 1 day After 2 days After 3 days After 4 days

Formulated liquid 1

4.67 4.64 4.57 4.53 4.57

Formulated liquid 2

5.52 5.47 5.61 5.75 -

Formulated liquid 3

5.19 5.14 5.12 4.84 4.75

Formulated liquid 4

5.91 6.36 5.71 - -

Formulated liquid 5

5.05 5.07 5.1 5.07 5.19

Formulated liquid 6

4.43 4.4 4.34 4.37 4.42

Formulated liquid 7

6.2 6.18 6.18 5.91 5.6

As shown in Table 2, each of the formulated liquid 1 (RKGME), the formulated liquid 2 ((RKGA), the formulated liquid 3 (RMEG) and the formulated liquid 4 (RAG) has a characteristic value in the potential of oxidoreduction The oxidation-reduction potential of formulated liquids 1 and 3, including a component of the extract of 10 Phellinus linteus, shows a practically constant value regardless of the passage of time.On the other hand, the oxidation-reduction potential of formulated liquids 2 and 4, including the agaric extract component decreases considerably over time.The potential for oxidation-reduction of the formulated liquid 5 (RHG) decreases over time, but remains in the middle, between that of the extract component of Phellinus linteus and the component of the extract of agáricas On the other hand, the potential of oxidization-reduction of the formulated liquid 6 15 (liquid extracted from Phellinus linteus alone) remains constant over time , while that of the formulated liquid 7 (liquid extracted from agarics alone) decreases considerably with time. From the results it can be concluded that a change in the potential for rust-reduction over time in liquids formulated 1 to 3 containing Phellinus linteus and liquids formulated 2 and 4 containing agarics corresponds to a change in the potential of rust-reduction over time in the formulated liquid 6 (liquid extracted from Phellinus linteus alone) and the

20 formulated liquid 7 (liquid extracted from agarics alone), respectively.

On the other hand, as shown in Table 3, the pH is almost stable over time in all formulated liquids, the pH of liquids formulated 1 to 4 at the time of preparation is weakly acidic within a range greater than 4.5 but less than 6.0, maintaining the value during the period of validity. The present inventor confirmed

25 that the formulated liquid 5 (RGK) has antitumor effect, hypoglycemic effect and cholesterol lowering effect, in addition to revealing that these physiological activities can be associated with the value of the oxidoreduction potential less than 330 mV (US Patent No. 6,746,675). A full text of the description in US Pat. No. 6,746,675 is a part of this description by appointment.

30 A fact that liquids formulated 1 to 4 can maintain their oxidizing-reduction potentials or a lower oxidizing-reduction potential without a significant increase at least against the passage of time (i.e., against oxidation) possibly indicates that these Formulated liquids have a reducing power.

From the results it has been proven that liquids formulated 1 to 4 are weakly acidic, do not alter a

35 cells live and have the potential for oxidization-reduction of less than 330 mV at the time the solution is prepared, so that physiological activity such as the antitumor effect and the hypoglycemic effect is recognized.

[Another typical procedure for preparing the composition of the present invention]

In the example, the hot water extract of the basidiomycete fungus and that of the root of an araliaceous plant are used, but other compositions can be addressed. For example, you can extract a

component from a natural product with other extraction procedures. As an example, a starting raw material is subjected to a certain extraction procedure to filter the extract component, which is evaporated under reduced pressure. The product is sterilized, dried and then sieved to give a powder.

5 The dry extract composition is prepared to a powder, a granule, a capsule and a tablet etc. For example, the extraction component is mixed with a binder to granulate and dry to a granule. The granule can be used as such, converted into a tablet or loaded into a capsule. An additional binder can be added before or after the granulation process of the extract component after drying. The extract component can be dried to load a capsule for encapsulation. Can also be

10 add other pharmaceutically acceptable additives. The additive is not limited, but includes one or more of two kinds of preservatives to prolong the half-life of the component.

Additionally, an effective component can be dissolved in a pharmaceutically acceptable solvent and filtered to charge in a vial. This blister can be sterilized. Additionally, others can be added to the solution

15 pharmaceutically acceptable additives. The additive is not limited, but includes one or more of two kinds of preservatives to prolong the half-life of the component.

After separation of an effective component, the isolated effective component can only be used as a therapeutic agent. The effective component can be identified and prepared in a chemically synthetic way. In this case,

The chemically synthetic effective component can be used in the form of a powder, a granule, a capsule, a tablet or a blister etc., and provide other means for administering the composition to a patient. If necessary, other pharmaceutically acceptable additives may be added.

Claims (5)

one.

 A physiologically active composition, which contains:

a component of the extract of a carpophore of the following basidiomycete fungi: Ganoderma lucidum, Coriolus Versicolor and Phellinus linteus; and an extract component of a P. japonicus CA Meyer root belonging to the Araliaceae family, in which the ratio between Ganoderma Lucidum: Coriolus Versicolor: Phellinus Linteus: P. CA Meyer japonicus in the raw material for extraction is 1: 1 1: 1 by weight, in which the composition of a carpophore extract of the fungi basidiomycetes and the extract component of a root of. japonicus C.A. Meyer are, respectively, components of extract with hot water, and in which the oxidation-reduction potential of an aqueous solution of the composition is not greater than 330 mV.

2.

 The composition according to claim 1, wherein the pH of an aqueous solution of the composition is not less than 4.5 and not more than 6.5.

3.

 A pharmacological formulation that is mixed when used and provided with a first drug comprising an extract component of a Ganoderma lucidum, Coriolus Versicolor and Phellinus Linteus carpophore and a second drug comprising an extract component of a root of. CA Meyer japonicus, in which the ratio between Ganoderma Lucidum: Coriolus Versicolor: Phellinus Linteus: P. japonicus CA Meyer in the raw material for extraction is 1: 1: 1: 1 by weight, in which the extract composition of a Carpophore of basidiomycete fungi and the extract component of a root of P. japonicus CA Meyer are, respectively, components of extract with hot water, and in which the oxidation-reduction potential of an aqueous solution of the composition is not greater than 330 mV.

Four.

 A process for preparing a physiologically active composition according to any one of claims 1 to 3, said process comprising the steps of extracting with a hot water a carpophore of Ganoderma lucidum and Coriolus Versicolor, with hot water extracting a carpophore of Phellinus linteus, extract a root of P. japonicus CA Meyer with hot water, in which the ratio between Ganoderma Lucidum: Coriolus Versicolor: Phellinus Linteus: P. japonicus CA Meyer in the raw material for extraction is 1: 1: 1: 1 by weight and mix the extract components with the hot water obtained in the extraction stages.

5.

 A method of preparing a physiologically active composition according to any one of claims 1 to 3, said process comprising the steps of:

obtain a hot water extract of a Ganoderma lucidium and Coriolus Versicolor carpophore, a hot water extract of a Phellinus linteus carpophore and a hot water extract of a P. japonicus CA Meyer root separately or from the same extraction system with respect to at least more than two kinds of hot water extracts, so that a composition comprising the hot water extract component of a carpophore of a fungus belonging to Ganoderma Lucidum and Coriolus Versicolor, the extract component is prepared in hot water of a carhell of Phellinus Linteus and the component of hot water extract of a root of P. japonicus CA, in which the ratio between Ganoderma Lucidum: Coriolus Versicolor: Phellinus Linteus: P. japonicus CA Meyer in the raw material for extraction is 1: 1: 1: 1 by weight.